Method for producing 3,7-diaza-bicyclo[3.3.1]nonane compounds
View Patent ↗The invention relates to a one-pot reaction for the production of 3,7-diaza-bicyclo[3.3.1]nonane compounds, wherein in a first step a dicarboxylic acid ester is reacted with a pyridine aldehyde and a primary amine. The piperidone created in this manner is reacted with formaldehyde and a further primary amine in a second step. It is essential to the invention that both reaction steps are carried out in a one-pot variation in a C 1 -C 4 alcohol as the solvent, and that the reaction water created is removed by means of distillation.
1. A method for producing a 3,7-diazabicyclo[3.3.1]nonane compound of the formula 1
where
R is hydrogen, hydroxyl, C 1 -C 4 -alkyl;
R 1 is C 1 -C 4 -alkyl, C 6 -C 10 -aryl, pyridinyl-C 1 -C 4 -alkyl;
R 2 is C 1 -C 4 -alkyl, C 6 -C 10 -aryl;
R 3 is C 1 -C 4 -alkyl and
X is C═O or C(OH) 2 ,
comprising the steps of
(a) reacting a dicarboxylic acid ester of the formula (2)
with a pyridinealdehyde of the formula (3)
and also an amine of the formula (4)
R 2 —NH 2 (4)
to give a piperidone of the formula (5)
and
(b) reacting the piperidones of the formula (5) obtained in this way with formaldehyde and an amine of the formula R 1 —NH 2 , where R, R 1 , R 2 and R 3 are defined above, wherein the reaction stages (a) and (b) are carried out in a C 1 -C 4 -alcohol and the water of reaction that is formed in each case is removed by azeotropic distillation, where, at the same time, a C 1 -C 4 -alcohol is metered in, wherein the reaction stages (a) and (b) are carried out in a one-pot method without isolation of the intermediate product (5).
2. A method as claimed in claim 1 , wherein the reaction stages (a) and (b) are carried out in a branched C 3 - or C 4 -alcohol.
3. A method as claimed in claim 1 , wherein the reaction stages (a) and (b) are carried out in isobutanol.